Pyrazinamide-derived hydrazone outperforms pyrazinamide activity in Mycobacterium tuberculosis DM97: an in vitro and in silico study

Paucar C.A.; Alvarado-Huayhuaz J.; Vega H.G.; Rocio R.P.; Peralta M.Z.; Cortavarria P.S.; Negrón A.V. · Ecletica Quimica (2026) · DOI: 10.26850/1678-4618.eq.v51.2026.e1506

Resumen

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (MTB). Pyrazinamide (PZA) is a prodrug used in first-lines treatment. New drugs proposals are urgent, given the increased resistance to antimicrobials such as PZA. In this work, we have synthesized and characterized N'-[(1E)-(4-nitrophenyl)methylidene]pyrazine-2-carbohydrazide (C3), to evaluate its antituberculosis activity in vitro in MTB H37Rv (wild type) and DM97 (PZA resistant). C3 was synthesized and characterized by FT-IR and 1H/13C NMR, among others. C3 is a hydrazone derived from PZA. Both compounds have an analogous and stable docking with the pyrazinamidase enzyme, according to our in-silico studies. In the tetrazolium microplate assay (TEMA) performed on MTB H37Rv at pH 6.0 and 6.8, it was found that PZA has greater antituberculosis activity than C3 on H37Rv, however, in DM97, C3 (MIC = 128 μg/mL at pH 6.0) presented greater antituberculosis activity than PZA (MIC > 800 μg/mL at pH 6.0), which demonstrates the antituberculosis potential of C3 against this strain resistant to PZA.

Instituciones: Universidad Peruana Cayetano Heredia; Universidad Nacional de Ingeniería